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. 2016 Sep:69:78-91.
doi: 10.1016/j.jmgm.2016.08.011. Epub 2016 Aug 28.

In-silico screening for anti-Zika virus phytochemicals

Kendall G Byler  1 , Ifedayo Victor Ogungbe  2 , William N Setzer  3
Affiliations

In-silico screening for anti-Zika virus phytochemicals

Kendall G Byler et al. J Mol Graph Model. 2016 Sep.

Abstract

Zika virus (ZIKV) is an arbovirus that has infected hundreds of thousands of people and is a rapidly expanding epidemic across Central and South America. ZIKV infection has caused serious, albeit rare, complications including Guillain-Barré syndrome and congenital microcephaly. There are currently no vaccines or antiviral agents to treat or prevent ZIKV infection, but there are several ZIKV non-structural proteins that may serve as promising antiviral drug targets. In this work, we have carried out an in-silico search for potential anti-Zika viral agents from natural sources. We have generated ZIKV protease, methyltransferase, and RNA-dependent RNA polymerase using homology modeling techniques and we have carried out molecular docking analyses of our in-house virtual library of phytochemicals with these protein targets as well as with ZIKV helicase. Overall, 2263 plant-derived secondary metabolites have been docked. Of these, 43 compounds that have drug-like properties have exhibited remarkable docking profiles to one or more of the ZIKV protein targets, and several of these are found in relatively common herbal medicines, suggesting promise for natural and inexpensive antiviral therapy for this emerging tropical disease.

Keywords: Homology model; Molecular docking; Neglected tropical disease; Zika virus.

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
Ligand-receptor interaction map of Bz-Nle-Lys-Arg-Arg-H with the West Nile virus NS2B-NS3 protease (PDB 2FP7) (panel A) and homology-modeled Zika virus NS2B-NS3 protease (panel B).
Fig. 2
Fig. 2
Lowest-energy docked poses of flinderoles A and B with ZIKV NS2B-NS3 protease. The hydrophobic cavity is shown with green hashmarks.
Fig. 3
Fig. 3
Ligand-receptor interaction map of angusticornin B (panel A) and kuraridin (panel B) with the Zika virus NS2B-NS3 protease.
Fig. 4
Fig. 4
Ligand-receptor interaction map of cassiarin D with the with the ATP binding site (panel A) and 4,4′-dimethylisoborreverine (panel B) and with the RNA binding site of the Zika virus NS3 helicase (PDB 5JMT [23]).
Fig. 5
Fig. 5
Protein-ligand interaction map between Zika virus NS5 methyltransferase and the lowest-energy docked pose of the phenolic ligand cimiracemate B (panel A) and the lignan (−)-asarinin (panel B).
Fig. 6
Fig. 6
Ribbon structure of Zika virus NS5 RNA-dependent RNA polymerase homology model based on the Japanese encephalitis virus NS5 (PDB 4K6 M [30]). The binding cavity is shown in green with the preferred ligand docking sites, A–D.
Fig. 7
Fig. 7
Protein-ligand interaction map between Zika virus NS5 RNA-dependent RNA polymerase and the lowest-energy docked pose of the prenylated chalcone, 2′,4,4′-trihydroxy-3,3′-diprenylchalcone (panel A), the bis-indole alkaloid flinderole B (panel B), the polyphenoic compound 4′,7-digalloylcatechin (panel C), and the lignan di-O-demethylisoguaiacin (panel D).
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